Autoimmune hepatitis

Epidemiology

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Etiology

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• AIH is commonly associated with other autoimmune conditions
  • Type 1 AIH: Hashimoto thyroiditis, Grave disease, ulcerative colitis, celiac disease, rheumatoid arthritis
  • Type 2 AIH: Hashimoto thyroiditis, type 1 diabetes mellitus, vitiligo

Pathophysiology

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Classification

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• Type 1 AIH (80% of cases): characteristic autoantibodies include antinuclear antibodies (ANAs), anti-smooth muscle antibodies (ASMAs) anti-soluble liver antigen antibodies (anti-SLA)
• Type 2 AIH: characteristic autoantibodies include anti-liver-kidney microsomal-1 antibodies (anti-LKM-1), anti-liver cytosol antibodies-1 (ALC-1)

Clinical features

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Autoimmune Liver Diseases

Mnemonic

• PBC: Boobs, Women get it (autoimmune + mitochondria from mom) → “Women stay inside” (intrahepatic ducts only).
• PSC: Scrotom, Men get it → “Men go wherever” (intra- and extrahepatic ducts) + p-ANCA (“perineuclear” → crude link to male anatomy).

Feature	Primary Sclerosing Cholangitis (PSC)	Primary Biliary Cholangitis (PBC)	Autoimmune Hepatitis (AIH)
Patho	Inflammation/fibrosis of intra- & extrahepatic bile ducts	Autoimmune destruction of intrahepatic bile ducts	Autoimmune destruction of hepatocytes
Epi / Assoc.	M > F (2:1), <40s Assoc: Ulcerative Colitis (IBD) (>80%)	F >> M (9:1), 40-60s Assoc: Sjögren’s, other autoimmune dz	F > M (3:1), bimodal (young/middle-aged) Assoc: Other autoimmune dz
Labs	Cholestatic: ↑↑ ALP, ↑ GGT	Cholestatic: ↑↑ ALP, ↑ GGT	Hepatocellular: ↑↑↑ AST/ALT (>1000s common), ↑ IgG
Serology	(+) p-ANCA	(+) AMA (Anti-Mitochondrial Ab)	(+) ANA, (+) ASMA (Anti-Smooth Muscle Ab)
Dx / Histo	MRCP/ERCP: “Beads on a string” Histo: “Onion skinning” periductal fibrosis	Normal imaging Histo: Florid duct lesion (lymphocytic cholangitis, granulomas)	Normal/nonspecific imaging Histo: Interface hepatitis, plasma cells
Tx	Symptomatic Tx; Liver transplant (definitive)	Ursodeoxycholic acid (UDCA)	Corticosteroids, Azathioprine
Key Risk	Cholangiocarcinoma, Colorectal Cancer (w/ UC)	Osteoporosis, Cirrhosis, HCC	Cirrhosis, Acute Liver Failure

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• Nonspecific symptoms
  • Fatigue
  • Upper abdominal pain
  • Weight loss
• Signs of acute liver failure (∼ ⅓ of patients)

Diagnostics

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Laboratory tests

• Key Labs:
  • Significant elevation of ALT and AST (often > 10x ULN).
  • Hypergammaglobulinemia (specifically ↑ IgG levels). c
  • Bilirubin and ALP/GGT are mildly elevated (unless overlap syndrome).
• Serology (High-Yield USMLE Distinction):
  • Type 1 (Most common, adults): (+) ANA (anti-nuclear antibody) and/or (+) ASMA (anti-smooth muscle antibody).
  • Type 2 (Pediatric/Young adult, aggressive): (+) Anti-LKM-1 (anti-liver-kidney microsomal-1) and/or (+) Anti-LC-1 (anti-liver cytosol-1).
• Confirmatory/Gold Standard: Liver Biopsy.
  • Key histopathologic finding: Interface hepatitis (piecemeal necrosis/lymphoplasmacytic infiltrate invading the limiting plate).
  • Abundant plasma cell infiltrate in portal tracts.
    • Therefore ↑ IgG levels
  • Hepatocyte rosette formation.
• Imaging:
  • RUQ Ultrasound: Used initially to rule out biliary obstruction; typically normal or shows non-specific parenchymal changes.

Liver biopsy

• Histological findings:
  • Lymphoplasmacytic interface hepatitis: ongoing inflammatory process with lymphocytic infiltration, bridging or multiacinar necrosis, and fibrotic changes
  • Bile duct changes (e.g., cholangitis, ductal injury)

Treatment

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